Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003768055 | SCV000817453 | uncertain significance | Familial adenomatous polyposis 1 | 2024-01-03 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2464 of the APC protein (p.Ser2464Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 569210). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Mendelics | RCV003492129 | SCV000838147 | likely benign | Hereditary cancer | 2024-01-23 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000776331 | SCV000911683 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-20 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with cysteine at codon 2464 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV000776331 | SCV001188736 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-24 | criteria provided, single submitter | clinical testing | The p.S2464C variant (also known as c.7391C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 7391. The serine at codon 2464 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478409 | SCV004220558 | uncertain significance | not provided | 2023-02-10 | criteria provided, single submitter | clinical testing | To the best of our knowledge, the variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000013 (2/152214 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
| All of Us Research Program, |
RCV003999536 | SCV004835673 | uncertain significance | Classic or attenuated familial adenomatous polyposis | 2023-10-30 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003768055 | SCV005052441 | uncertain significance | Familial adenomatous polyposis 1 | 2023-12-01 | criteria provided, single submitter | clinical testing |